Meeting Abstract
S2.2 Monday, Jan. 4 Metabolic Function and Aging in Yeast VAN VOORHIES, W.A.*; GOTTSCHLING, D.E.; New Mexico State University; Fred Hutchinson Cancer Research Center wvanvoor@nmsu.edu
The most widely proposed mechanistic explanation for the aging process links the production of free-radicals and other oxidants produced during aerobic respiration to biomolecular damage that results in aging. While the scientific origins of this concept extends back nearly 100 years, considerable controversy currently exists regarding the importance of metabolic rate to longevity. We are pursing another potential explanation for aging-the increase in genomic instability that occurs during aging. This phenomenon has been most extensively characterized in the budding yeast, Saccharomyces cerevisiae, in which there is a large increase in the rate at which genetic heterozygosity is lost in the daughter cells of aging mother cells. Recent research indicates that the age-induced increase in genomic instability may be caused by defects in the biogenesis of iron sulfur clusters (ISC) in the mitochondria. These defects produce cells that are unable to carry-out oxidative phosphorylation because of damage to mitochondrial DNA. This mitochondrial dysfunction may lead to increased rates of genomic instability and a loss of respiratory capacity. Yeast cells in this state experience a crisis in which they show reduced growth rates, high rates of cell cycle arrest, and an increase in nuclear genome instability. This is thought to be caused by a reduction in the mitochondrial inner membrane potential which causes defects in molecular transport into and out of the mitochondria, affecting ISC biogenesis. We will present the results of experiments in which we track the localization of fluorescently labeled ISC proteins for yeast grown on different metabolic substrates and as cells recover from the metabolic crisis induced by a loss of mitochondrial DNA. Additionally we will discuss the affects of mutations in ISC proteins on yeast metabolic function.
